An extensive evaluation has been undertaken of patients with auto-immune lympho-proliferative syndrome (ALPS) and their extended-family members, based on characterization of the expanded double negative T-cell and B- cell populations. To date the double negative T-cells have been demonstrated to be alpha beta TcR, CD57+, HLA-DR+, and CD45RA+. In addition, a number of asymptomatic family members appear to have an increased level of double negative T-cells.